723/726 Proof of Concept Study in Allergen Challenge Chamber in Hannover

Phase 2

Completed

Conditions: Rhinitis, Allergic, Seasonal

Interventions: Drug: GSK835726 10mg
Drug: GSK1004723 1000mcg
Drug: Cetirizine 10mg
Drug: placebo

Registration Number: NCT00972504

Lead Sponsor: GlaxoSmithKline

Brief Summary: This is a randomised, double-blind, placebo-controlled 4-period cross-over study to assess the efficacy and safety of repeat dose intranasal GSK1004723 (1000µg), oral GSK835726 (10mg) and cetirizine (10mg) in the environmental challenge chamber in subjects with seasonal allergic rhinitis.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 54

Inclusion Criteria

Subject is healthy apart from seasonal allergic rhinitis, as determined by a physician. Can have mild asthma.
Males or female using contraceptives
Aged 18 - 65
Weight 50kg+, BMI 19-32 kg/m2
Exhibit response to Challenge Chamber and skin prick test.
Non-smoker
Capable of giving informed consent
AST and ALT<2xULN; alkaline phosphatase and bilirubin <or=1.5xULN

Exclusion Criteria

No nasal structural abnornmality/polyposis, surgery, infection.
any respiratory disease, other than mild asthma or seasonal allergic rhinitis
participated in another clinical study within 30 days.
Subject has donated a unit of blood within 1 month
Use of prescription or non-prescription drugs, including vitamins and st john's wort within 7 days of trial.
History of sensitivty to drug
History of alcohol/drug abuse within 12 months.
Positive Hepatitis B antibody test
Positive HIV antibody test
Risk of non-compliance with study protocol
Pregnant or llactating females
Perenial allergic rhinitis
Administration of oral, injectable or dermal corticosteriods within 8 weeks, intranasal or inhaled within 3 weeks.
Past or present disease that may affect outcome, as judge by investigator
Specific Immunotherapy within 2 years

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
GSK835726 (10mg)	GSK835726 10mg	10mg oral dose
GSK1004723 (1000mcg)	GSK1004723 1000mcg	1000mcg nasal spray solution
Cetirizine 10mg	Cetirizine 10mg	10mg cetirizine as active comparator
placebo	placebo	placebo

Primary Outcome Measures

Name	Time	Method
Weighted Mean TNSS (Sneeze, Itch, Rhinorrhoea and Nasal Blockage) 1-6 Hours Post Start of Allergen Challenge (2-7 Hours Post-dose) on Day 3	Day 3 of each treatment period (approximately up to 63 days)	On the third dosing day, participants entered the ECC for a duration of 6 hours, 1 hour after receiving their third dose. Time 0 hour was considered as the time that the participant entered the ECC. Nasal blockage, itch, sneeze and rhinorrhoea was scored on a categorical scale from 0 to 3 (0: no symptoms; 1: mild symptoms; 2: moderate symptoms; 3: severe symptoms). The total TNSS ranged from 0-12 point, with low score indicates well-being and higher score indicates more severity. Individual symptoms scores was summed at each time point (0, 20, 40, 60, 80, 100, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300, 320, 340 and 360 minutes). The adjusted mean is provided as least square mean.

Secondary Outcome Measures

Name	Time	Method
Mean Forced Expiratory Volume in 1 Second (FEV1)	Day 3 of each treatment period (approximately up to 63 days)	On the third dosing day, participants entered the ECC for a duration of 6 hours, 1 hour after receiving their third dose. Time 0 hour was considered as the time that the participant entered the ECC. FEV1 was measured at pre-challenge, 60, 120, 180, 240, 300 and 360 minutes.
Weighted Mean of the Individual Components of TNSS (Sneeze, Itch, Rhinorrhoea and Nasal Blockage) 1-6 Hours Post Start of Allergen Challenge (2-7 Hours Post-dose) on Day 3	Day 3 of each treatment period (approximately up to 63 days)	On the third dosing day, participants entered the ECC for a duration of 6 hours, 1 hour after receiving their third dose. Time 0 hour was considered as the time that the participant entered the ECC. Nasal blockage, itch, sneeze and rhinorrhoea was scored on a categorical scale from 0 to 3 (0: no symptoms; 1: mild symptoms; 2: moderate symptoms; 3: severe symptoms). The total TNSS ranged from 0-12 point, with low score indicates well-being and higher score indicates more severity. Individual symptoms scores was summed to produce the TNSS at each time point (0, 20, 40, 60, 80, 100, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300, 320, 340 and 360 minutes). The adjusted mean is provided as least square mean.
Weighted Mean Wet Tissue Weight (as a Surrogate Marker of Nasal Secretion) 1-6 Hours Post Start of Allergen Challenge (2-7 Hours Post-dose) on Day 3	Day 3 of each treatment period (approximately up to 63 days)	On the third dosing day, participants entered the ECC for a duration of 6 hours, 1 hour after receiving their third dose. Time 0 hour was considered as the time that the participant entered the ECC. Wet tissue weight assessments was measured as a surrogate marker of nasal secretion at 60, 120, 180, 240, 300 and 360 minutes. The adjusted mean is provided as least square mean.
Weighted Mean Nasal Congestion VAS 1-6 Hours Post Start of Allergen Challenge (2-7 Hours Post-dose) on Day 3	Day 3 of each treatment period (approximately up to 63 days)	On the third dosing day, participants entered the ECC for a duration of 6 hours, 1 hour after receiving their third dose. Time 0 hour was considered as the time that the participant entered the ECC. Nasal congestion was measured on 0-10 centimeter VAS scale (0: no symptoms and 10: the worst possible symptoms) with low score indicates well-being and higher values indicate greater congestion. It was measured at 60, 80, 100, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300, 320, 340 and 360 minutes. The adjusted mean is provided as least square mean.
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)	approximately up to 63 days	An AE was defined as any untoward medical occurrence (MO) in a participant temporally associated with the use of a medicinal product (MP), whether or not considered related to the MP and can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with its use. The SAE was any untoward MO that, at any dose, results in death, life threatening, persistent or significant disability/incapacity, results in or prolongs inpatient hospitalization, congenital abnormality or birth defect, that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention or is associated with liver injury and impaired liver function defined as: alanine aminotransferase \>=3 times upper limit of normal (ULN), and total bilirubin \>=2 times ULN or international normalized ratio more than 1.5.